Our experiments are designed to provide a better understanding of the generation, persistence and function of CD8 T cell memory and improve strategies for immunization against natural or engineered respiratory pathogens. In AIM 1. we will study the control and significance of memory cell heterogeneity. Memory cell populations are heterogeneous with respect to a number of properties but little is known about their relative functions. We will generate different subsets of memory populations and determine their persistence, location, function and ability to protect against viral challenge. We will further define the properties of the different subsets of memory T cells we generate and devise strategies to elicit the one(s) that provide the best protection. In AIM 2. We will study the interactions and competition between memory cell populations. In "real life" people are exposed to a number of different pathogen challenges and are vaccinated with multiple vaccines to protect against a multitude of diseases. Little is known of how the responses to one set of antigens may impact the response to others. Our goal is to define whether two memory populations compete or otherwise interact with one another and whether there is any interaction between naive and memory T cell populations. We will establish whether it is better to use vaccines with many epitopes or few, whether it is counter productive to immunize people against a large number of pathogens at the same time and whether there timing issues that affect whether immunization provides protection. In AIM 3. We will study the impact of antigen challenge on memory cell persistence. It has been shown that memory cells may be "used up" or exhausted on antigen challenge under certain conditions. We will determine what fraction of memory cells survive live virus challenge and what fraction of new memory cells arise de novo from naive cells under a number of conditions. This will provide important information about the function and limitations of memory T cells.